Claims for Patent: 9,884,039

Summary for Patent: 9,884,039

Title:	Pharmaceutical formulations for subcutaneous administration of furosemide
Abstract:	The present teachings relate to liquid pharmaceutical formulations of furosemide, where the pharmaceutical formulations include a molar excess of tris(hydroxymethyl)aminomethane to furosemide, have a pH in the range of 7 to 8.5, and a concentration of tris(hydroxymethyl)aminomethane greater than or equal to about 50 mM. The present teachings can improve the stability of liquid pharmaceutical formulations including furosemide and the suitability of such pharmaceutical formulations for subcutaneous administration or delivery.
Inventor(s):	Scott A. Michaels, Pieter Muntendam, Glenn R. Larsen
Assignee:	ScPharmaceuticals Inc
Application Number:	US14/781,706
Patent Claims:	1. A method of treating a patient with or exhibiting the symptoms of edema, hypertension or heart failure, the method comprising: administering to a patient a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation comprises: furosemide, or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein furosemide is the sole therapeutically active agent in the liquid pharmaceutical formulation and the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 15 mg/mL; and a pharmaceutically acceptable buffer comprising tris(hydroxymethyl)aminomethane, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 250 mM; wherein the liquid pharmaceutical formulation is isosmotic and has a pH between about 7.2 to about 8, and the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to two. 2. The method of claim 1, wherein administering comprises administering subcutaneously the pharmaceutical formulation. 3. The method of claim 2, wherein administering subcutaneously comprises using a pump device. 4. The method of claim 3, wherein the pump device is a patch device. 5. The method of claim 1, wherein administering comprises administering intravenously the liquid pharmaceutical formulation. 6. A method of treating a patient with or exhibiting the symptoms of edema, hypertension or heart failure, the method comprising: administering subcutaneously to a patient a liquid pharmaceutical formulation comprising: furosemide, or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein the liquid pharmaceutical formulation comprises about 8 mg/mL of furosemide, which is the sole therapeutically active agent; and a pharmaceutically acceptable buffer comprising tris(hydroxymethyl)aminomethane, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is about 50 mM; wherein the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is about 2, and the liquid pharmaceutical formulation has a pH of about 7.4 and is isosmotic. 7. The method of claim 1, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 10 mg/mL. 8. The method of claim 1, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 6 mg/mL to about 10 mg/mL. 9. The method of claim 6, wherein administering subcutaneously comprises using a pump device. 10. The method of claim 9, wherein the pump device is a patch device. 11. A method of treating a patient with or exhibiting the symptoms of edema, hypertension or heart failure, the method comprising: administering subcutaneously to a patient a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation comprises: furosemide, or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein furosemide is the sole therapeutically active agent in the liquid pharmaceutical formulation and the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 20 mg/mL; and a pharmaceutically acceptable buffer comprising tris(hydroxymethyl)aminomethane, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is greater than or equal to about 50 mM; wherein the liquid pharmaceutical formulation is isosmotic and has a pH between about 7 to about 8.5, and the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to 1.5. 12. The method of claim 11, wherein the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to two. 13. The method of claim 11, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 250 mM. 14. The method of claim 12, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 250 mM. 15. The method of claim 11, wherein the liquid pharmaceutical formulation has a pH between about 7.2 to about 8. 16. The method of claim 12, wherein the liquid pharmaceutical formulation has a pH between about 7.2 to about 8. 17. The method of claim 13, wherein the liquid pharmaceutical formulation has a pH between about 7.2 to about 8. 18. The method of claim 13, wherein the liquid pharmaceutical formulation has a pH between about 7.2 to about 8. 19. The method of claim 11, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 15 mg/mL. 20. The method of claim 12, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 15 mg/mL. 21. The method of claim 13, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 15 mg/mL. 22. The method of claim 15, wherein the amount of furosemide in the liquid pharmaceutical formulation is between about 2 mg/mL to about 15 mg/mL. 23. The method of claim 18, wherein administering subcutaneously comprises using a pump device.